Details for: RAE1

Gene ID: 8480

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: RAE1

Ensembl ID: ENSG00000101146

Description: ribonucleic acid export 1

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • club cell CL0000158
    CSI 8.38
    rCSI 12.27%
    PRS 71.64
  • vascular associated smooth muscle cell CL0000359
    CSI 6.43
    rCSI 20.87%
    PRS 75.13
  • type B pancreatic cell CL0000169
    CSI 4.73
    rCSI 10.48%
    PRS 76.31
  • fibroblast of lung CL0002553
    CSI 4.55
    rCSI 4.23%
    PRS 77.7
  • interstitial cell of Cajal CL0002088
    CSI 4.53
    rCSI 5.76%
    PRS 82.19
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 4.09
    rCSI 4.72%
    PRS 69.28
  • mesodermal cell CL0000222
    CSI 4.03
    rCSI 4.84%
    PRS 74.84
  • neural crest cell CL0011012
    CSI 3.81
    rCSI 3.01%
    PRS 65.23
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 3.51
    rCSI 2.67%
    PRS 89.05
  • double negative thymocyte CL0002489
    CSI 3.4
    rCSI 2.37%
    PRS 88.02
  • cerebral cortex GABAergic interneuron CL0010011
    CSI 3.36
    rCSI 9.91%
    PRS 78.32
  • naive T cell CL0000898
    CSI 3.33
    rCSI 2.31%
    PRS 90.55
  • CD4-positive, CD25-positive, alpha-beta regulatory T cell CL0000792
    CSI 3.22
    rCSI 3.16%
    PRS 90.23
  • intermediate monocyte CL0002393
    CSI 3.14
    rCSI 4.74%
    PRS 82.39
  • erythroid progenitor cell CL0000038
    CSI 3.13
    rCSI 17.93%
    PRS 83.12
  • epithelial cell of lung CL0000082
    CSI 2.97
    rCSI 2.46%
    PRS 77.61
  • Kupffer cell CL0000091
    CSI 2.9
    rCSI 6.62%
    PRS 77.9
  • immature B cell CL0000816
    CSI 2.79
    rCSI 2.07%
    PRS 87.89
  • rod bipolar cell CL0000751
    CSI 2.73
    rCSI 4.91%
    PRS 70.25
  • group 3 innate lymphoid cell CL0001071
    CSI 2.63
    rCSI 1.98%
    PRS 82.85
  • early lymphoid progenitor CL0000936
    CSI 2.49
    rCSI 2.19%
    PRS 82.13
  • ON-bipolar cell CL0000749
    CSI 2.47
    rCSI 3.68%
    PRS 77.33
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 2.4
    rCSI 2.44%
    PRS 87.12
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.4
    rCSI 4.23%
    PRS 57.89
  • interneuron CL0000099
    CSI 2.36
    rCSI 4.74%
    PRS 66.79
  • activated type II NK T cell CL0000931
    CSI 2.32
    rCSI 2.61%
    PRS 89.99
  • pro-B cell CL0000826
    CSI 2.26
    rCSI 1.87%
    PRS 79.52
  • hematopoietic stem cell CL0000037
    CSI 2.16
    rCSI 1.44%
    PRS 79.89
  • renal alpha-intercalated cell CL0005011
    CSI 2.12
    rCSI 2.84%
    PRS 83.76
  • plasmacytoid dendritic cell, human CL0001058
    CSI 2.08
    rCSI 1.45%
    PRS 80.35
  • pancreatic A cell CL0000171
    CSI 2.07
    rCSI 2.17%
    PRS 80.5
  • cerebral cortex endothelial cell CL1001602
    CSI 2.06
    rCSI 3.56%
    PRS 68.19
  • promyelocyte CL0000836
    CSI 2.06
    rCSI 2.96%
    PRS 83.54
  • radial glial cell CL0000681
    CSI 2.04
    rCSI 2.84%
    PRS 75.78
  • renal beta-intercalated cell CL0002201
    CSI 2.04
    rCSI 4.87%
    PRS 77.33
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.01
    rCSI 2.5%
    PRS 56.64
  • ionocyte CL0005006
    CSI 1.97
    rCSI 2.11%
    PRS 78.02
  • myeloid leukocyte CL0000766
    CSI 1.97
    rCSI 1.81%
    PRS 78.55
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 1.95
    rCSI 2.55%
    PRS 87.91
  • granulocyte monocyte progenitor cell CL0000557
    CSI 1.94
    rCSI 1.68%
    PRS 81.33
  • stem cell CL0000034
    CSI 1.92
    rCSI 1.86%
    PRS 69.84
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 1.92
    rCSI 1.73%
    PRS 75.04
  • ciliated epithelial cell CL0000067
    CSI 1.87
    rCSI 1.64%
    PRS 65.85
  • hepatocyte CL0000182
    CSI 1.82
    rCSI 3.27%
    PRS 76.34
  • intestinal epithelial cell CL0002563
    CSI 1.79
    rCSI 1.88%
    PRS 74.77
  • fallopian tube secretory epithelial cell CL4030006
    CSI 1.78
    rCSI 1.72%
    PRS 76.39
  • VIP GABAergic cortical interneuron CL4023016
    CSI 1.76
    rCSI 2.1%
    PRS 58.66
  • erythrocyte CL0000232
    CSI 1.75
    rCSI 3.98%
    PRS 78.03
  • keratinocyte CL0000312
    CSI 1.75
    rCSI 1.47%
    PRS 80.24
  • mesenchymal cell CL0008019
    CSI 1.75
    rCSI 4.44%
    PRS 70.42
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.73
    rCSI 3.89%
    PRS 59.41
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 1.72
    rCSI 2.21%
    PRS 73.3
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.71
    rCSI 2.2%
    PRS 59.93
  • enteric smooth muscle cell CL0002504
    CSI 1.61
    rCSI 2.3%
    PRS 78.1
  • placental villous trophoblast CL2000060
    CSI 1.58
    rCSI 2.45%
    PRS 76.16
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 1.55
    rCSI 1.19%
    PRS 79.58
  • retina horizontal cell CL0000745
    CSI 1.52
    rCSI 2.31%
    PRS 73.78
  • multi-ciliated epithelial cell CL0005012
    CSI 1.46
    rCSI 1.45%
    PRS 70.76
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.45
    rCSI 2.43%
    PRS 58.71
  • common myeloid progenitor CL0000049
    CSI 1.41
    rCSI 1.14%
    PRS 79.36
  • promonocyte CL0000559
    CSI 1.38
    rCSI 2.37%
    PRS 83.73
  • lung macrophage CL1001603
    CSI 1.34
    rCSI 2.99%
    PRS 84.38
  • peripheral nervous system neuron CL2000032
    CSI 1.33
    rCSI 1.81%
    PRS 68.43
  • glioblast CL0000030
    CSI 1.32
    rCSI 2.1%
    PRS 68.71
  • neural progenitor cell CL0011020
    CSI 1.31
    rCSI 5.74%
    PRS 65.61
  • lung ciliated cell CL1000271
    CSI 1.28
    rCSI 1.48%
    PRS 68.84
  • progenitor cell CL0011026
    CSI 1.17
    rCSI 2.48%
    PRS 71.65
  • germinal center B cell CL0000844
    CSI 1.05
    rCSI 3.13%
    PRS 87.65
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.92
    rCSI 2.86%
    PRS 60.41
  • retinal cone cell CL0000573
    CSI 0.88
    rCSI 1.41%
    PRS 66.8
  • large pre-B-II cell CL0000957
    CSI 0.86
    rCSI 2.45%
    PRS 83.5
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 0.84
    rCSI 4.22%
    PRS 88.54
  • primitive red blood cell CL0002355
    CSI 0.79
    rCSI 4.24%
    PRS 84.24

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [RAE1](/details-gene/8480) (Ribonucleic Acid Export 1) is a protein-coding gene located on chromosome 20q13.31. It functions as a key component of the nucleocytoplasmic transport machinery, primarily involved in the export of poly(A)+ RNA from the nucleus to the cytoplasm ([Link](https://doi.org/10.1016/s0378-1119(97)00322-3)). In addition to its role in [mRNA export from nucleus](/details-go/GO:0006406), [RAE1](/details-gene/8480) is critically involved in fundamental cellular processes including [cell division](/details-go/GO:0051301) and mitotic spindle formation ([Link](https://doi.org/10.1073/pnas.0609582104)). Its expression is significant across a wide range of cell types, with particularly high importance in metabolically active cells such as [club cells](/details-cell/CL0000158), [vascular associated smooth muscle cells](/details-cell/CL0000359), and [type B pancreatic cells](/details-cell/CL0000169), suggesting a ubiquitous yet vital role in maintaining cellular homeostasis and proliferation. ## Cellular Roles and Expression Landscape The **Overall** expression profile of [RAE1](/details-gene/8480) indicates its fundamental importance across diverse cell lineages. It shows the highest significance in secretory epithelial cells like [club cells](/details-cell/CL0000158) of the lung and endocrine [type B pancreatic cells](/details-cell/CL0000169), which are characterized by high rates of protein synthesis and export, consistent with the gene's primary function. High significance is also observed in contractile cells ([vascular associated smooth muscle cell](/details-cell/CL0000359)) and structural cells ([fibroblast of lung](/details-cell/CL0002553)), likely reflecting the constant transcriptional turnover required to maintain their function. Furthermore, [RAE1](/details-gene/8480) is significant in various progenitor and developing cell populations, including [neuroblasts (sensu Nematoda and Protostomia)](/details-cell/CL0000338), [mesodermal cells](/details-cell/CL0000222), and [erythroid progenitor cells](/details-cell/CL0000038). This pattern, coupled with its established role in the cell cycle, suggests that [RAE1](/details-gene/8480) is essential for cellular proliferation and differentiation during development. The gene also plays a role within the immune system, showing notable significance in lymphocyte populations such as [effector CD8-positive, alpha-beta T cells](/details-cell/CL0001050), [naive T cells](/details-cell/CL0000898), and [CD4-positive, CD25-positive, alpha-beta regulatory T cells](/details-cell/CL0000792), which aligns with the need for rapid RNA processing during immune activation and clonal expansion. ## Pathways and Molecular Function The functional annotations for [RAE1](/details-gene/8480) confirm its dual role in RNA transport and cell cycle regulation. It is a core component of [nucleocytoplasmic transport](/details-go/GO:0006913), localizing to the [nuclear pore](/details-go/GO:0005643) and participating directly in the [transport of mature mRNA to the cytoplasm](/details-pathway/R-HSA-72202). This fundamental process is essential for all gene expression. Beyond this canonical function, [RAE1](/details-gene/8480) is deeply integrated into the mechanics of the [Cell cycle, mitotic](/details-pathway/R-HSA-69278) pathway. It is involved in the [regulation of mitotic spindle organization](/details-go/GO:0060236) through its interaction with the nuclear mitotic apparatus protein (NuMA), a process critical for accurate chromosome segregation during [M phase](/details-pathway/R-HSA-68886) ([Link](https://doi.org/10.1073/pnas.0609582104)). The deubiquitination of [RAE1](/details-gene/8480) by USP11 has also been shown to be a key regulatory step for bipolar spindle formation ([Link](https://doi.org/10.1371/journal.pone.0190513)). Notably, the host cell transport machinery mediated by [RAE1](/details-gene/8480) is a frequent target for viral hijacking. Reactome pathways highlight its involvement in numerous [infectious diseases](/details-pathway/R-HSA-5663205), including [HIV infection](/details-pathway/R-HSA-162906), [Influenza infection](/details-pathway/R-HSA-168255), and [SARS-CoV-2 infection](/details-pathway/R-HSA-9694516). Recent studies have demonstrated that the SARS-CoV-2 Orf6 protein antagonizes interferon signaling by interacting with the RAE1-NUP98 complex, thereby disrupting nuclear import of key transcription factors like STAT1 ([Link](https://doi.org/10.1073/pnas.2016650117), [Link](https://doi.org/10.1128/mbio.00065-21)). This illustrates that [RAE1](/details-gene/8480) is a critical nexus for host-pathogen interactions. ## Research Directions The central role of [RAE1](/details-gene/8480) in both essential cellular processes and viral pathogenesis presents several avenues for future investigation. **Proposed Hypotheses:** 1. Given its high significance in progenitor cells and its critical function in mitotic spindle assembly, dysregulation of [RAE1](/details-gene/8480) expression or function in specific cancer types may be a driver of aneuploidy. The level of [RAE1](/details-gene/8480) expression could correlate with chromosomal instability and serve as a prognostic marker in rapidly dividing tumors. 2. The interaction of [RAE1](/details-gene/8480) with viral proteins like SARS-CoV-2 Orf6 suggests it may be a broadly utilized target for viral immune evasion. It is hypothesized that a range of other viruses, particularly those that replicate in the nucleus, have evolved proteins that similarly disrupt the RAE1-NUP98 complex to inhibit host antiviral responses or facilitate the export of viral ribonucleoproteins. **Experimental Approach:** To test the second hypothesis, a targeted protein-protein interaction screen could be employed. [RAE1](/details-gene/8480) could be used as bait in an affinity purification-mass spectrometry (AP-MS) experiment within cells systematically expressing individual proteins from a library of diverse viral pathogens (e.g., herpesviruses, adenoviruses, papillomaviruses). Hits would be validated in co-immunoprecipitation assays. Functionally, the impact of these novel interactions on host gene expression could be assessed using a reporter system for interferon-stimulated gene activation, determining if the viral protein phenocopies the inhibitory effect seen with SARS-CoV-2 Orf6. **Therapeutic Potential:** As [RAE1](/details-gene/8480) is essential for host cell viability, it is not a suitable target for direct inhibition. However, the specific protein-protein interaction interfaces between [RAE1](/details-gene/8480) and viral proteins represent highly attractive therapeutic targets. A strategy focused on developing small molecules or peptide mimetics that specifically block the binding of a viral antagonist (e.g., Orf6) to the RAE1-NUP98 complex could be pursued. Such a therapeutic would function as a host-directed antiviral, restoring the cell's intrinsic immune signaling pathways and inhibiting viral replication without the toxicity associated with globally disrupting nucleocytoplasmic transport.

Genular Protein ID: 2474784309

Symbol: RAE1L_HUMAN

Name: Rae1 protein homolog

UniProtKB Accession Codes:

P78406 A8K882 O15306 Q3SYL7 Q5TCH8 Q6V708 Q9H100 Q9NQM6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 ComplexPortal 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 12 Ensembl 3 EvolutionaryTrace 1 ExpressionAtlas 1 GO 17 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 6 PDBsum 6 PRINTS 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 28 RefSeq 6 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TCDB 1 TopDownProteomics 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9370289

Title: The human RAE1 gene is a functional homologue of Schizosaccharomyces pombe rae1 gene involved in nuclear export of poly(A)+ RNA.

PubMed ID: 9370289

DOI: 10.1016/s0378-1119(97)00322-3

PubMed ID: 9256445

Title: mRNA binding protein mrnp 41 localizes to both nucleus and cytoplasm.

PubMed ID: 9256445

DOI: 10.1073/pnas.94.17.9119

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 11780052

Title: The DNA sequence and comparative analysis of human chromosome 20.

PubMed ID: 11780052

DOI: 10.1038/414865a

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 17172455

Title: Rae1 interaction with NuMA is required for bipolar spindle formation.

PubMed ID: 17172455

DOI: 10.1073/pnas.0609582104

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 25944712

Title: N-terminome analysis of the human mitochondrial proteome.

PubMed ID: 25944712

DOI: 10.1002/pmic.201400617

PubMed ID: 29293652

Title: USP11 deubiquitinates RAE1 and plays a key role in bipolar spindle formation.

PubMed ID: 29293652

DOI: 10.1371/journal.pone.0190513

PubMed ID: 22357847

Title: RAE-1, a novel PHR binding protein, is required for axon termination and synapse formation in Caenorhabditis elegans.

PubMed ID: 22357847

DOI: 10.1523/jneurosci.2901-11.2012

PubMed ID: 33097660

Title: SARS-CoV-2 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling.

PubMed ID: 33097660

DOI: 10.1073/pnas.2016650117

PubMed ID: 33360543

Title: Overexpression of SARS-CoV-2 protein ORF6 dislocates RAE1 and NUP98 from the nuclear pore complex.

PubMed ID: 33360543

DOI: 10.1016/j.bbrc.2020.11.115

PubMed ID: 33849972

Title: SARS-CoV-2 ORF6 Disrupts Bidirectional Nucleocytoplasmic Transport through Interactions with Rae1 and Nup98.

PubMed ID: 33849972

DOI: 10.1128/mbio.00065-21

PubMed ID: 20498086

Title: Structural and functional analysis of the interaction between the nucleoporin Nup98 and the mRNA export factor Rae1.

PubMed ID: 20498086

DOI: 10.1073/pnas.1005389107

Sequence Information:

  • Length: 368
  • Mass: 40968
  • Checksum: 89A99C34BA668A97
  • Sequence:
    • MSLFGTTSGF GTSGTSMFGS ATTDNHNPMK DIEVTSSPDD SIGCLSFSPP TLPGNFLIAG 
SWANDVRCWE VQDSGQTIPK AQQMHTGPVL DVCWSDDGSK VFTASCDKTA KMWDLSSNQA 
IQIAQHDAPV KTIHWIKAPN YSCVMTGSWD KTLKFWDTRS SNPMMVLQLP ERCYCADVIY 
PMAVVATAER GLIVYQLENQ PSEFRRIESP LKHQHRCVAI FKDKQNKPTG FALGSIEGRV 
AIHYINPPNP AKDNFTFKCH RSNGTNTSAP QDIYAVNGIA FHPVHGTLAT VGSDGRFSFW 
DKDARTKLKT SEQLDQPISA CCFNHNGNIF AYASSYDWSK GHEFYNPQKK NYIFLRNAAE 
ELKPRNKK